Background. The etiology of long-lasting adverse reactions to gel fillers used in cosmetic surgery is not known. Bacterial infection and immunological reaction to the product have been suggested. Methods. We performed a case-control study, with 77 biopsies and 30 cytology specimens originating from 59 patients with adverse reactions to polyacrylamide gel, and 54 biopsies and 2 cytology specimens from 28 control subjects with no adverse reactions. Samples from 5 patients and 4 controls could not be investigated for presence of bacteria owing to limited material. Samples from the remaining 54 patients and 24 controls were systematically examined for the presence of bacteria by culture, 16S rRNA gene sequencing, Gram stain, and fluorescence in situ hybridization. Results. Bacteria, mostly normal skin bacteria such as Staphylococcus epidermidis and Propionibacterium acnes, were identified in bacteriologically investigated samples from 53 of 54 patients (98%), and in none of the 24 controls (0%). The bacteria were lying in small clusters, which in symptomatic lesions were detected up to 5 years postinjection. Conclusions. Commensal bacteria of low virulence are capable of producing long-term infection in the presence of polyacrylamide filler in cosmetic surgery, possibly due to a biofilm mode of growth. Adequate skin preparation and use of sterile technique in these procedures are mandatory, but antibiotic prophylaxis prior to injection of nondegradable gels like polyacrylamide should be explored as well.